Angiogenesis, the development and growth of new blood vessels, is important for organ development, wound healing and various pathological conditions such as tumor growth or proliferative retinopathies. Neovascularization depends on integrin-mediated adhesive contacts of the endothelial cells with the extracellular matrix as well as on the function of growth factors. There is emerging evidence that inflammatory cells, and particularly neutrophils, regulate endothelial cell functions related to angiogenesis. The participation of inflammatory cells in angiogenesis may depend on the biological context. Both pro-angiogenic and anti-angiogenic activities of neutrophils have been described. Neutrophils are a source of growth factors and proteases. However, neutrophil can generate the anti-angiogenic factors angiostatin and alpha-defensin. 1) We could show that alpha-defensins form a ternary complex with fibronectin (FN) and alpha5beta1-integrin and transform the FN-alpha5beta1-integrin interaction to one that does not promote endothelial cell adhesion. alpha-defensins thereby interfered with endothelial cell functions related to angiogenesis in vitro and in vivo. 2) The anti-angiogenic factor angiostatin was identified as a ligand of the leukocyte beta2-integrin Mac-1. Angiostatin was thereby found to exert an anti-inflammatory action by inhibiting leukocyte recruitment in vitro and in vivo. 3) CCN1 is an immediate early gene that acts as a ligand of alphavbeta3-integrin. We could demonstrate that VEGF upregulates CCN1 in osetoblasts and this CCN1 acts to attract endothelial cells and to assist in neovascularization in the context of repair angiogenesis. 4) The interaction between complement components C3 and C5 in hypoxia-driven angiogenesis is currently under investigation by using complement inhibitors and genetically modified mice. 5) Hypoxia induces replication arrest in cells. Nevertheless, in hypoxia-induced angiogenesis, such as during retinopathy of prematurity, endothelial cells need to actively proliferate due to the presence of hypoxia-inducible factors. To understand this paradox we study the DNA damage response to hypoxia in endothelial cells. Hypoxia induced a rapid DNA-damage response in endothelial cells accompanied by phosphorylated H2AX (&#947;-H2AX). in vitro and in vivo studies revealed that H2AX functions to help endothelial cells overcome the hypoxia induced replication arrest, thus identifying a novel crosstalk between the DNA repair response and hypoxia-driven angiogenesis.